Pub Date : 2026-02-01Epub Date: 2025-12-08DOI: 10.1016/j.tjnut.2025.101258
Wenli Zhao, Yuedong Shen, Xuan Wang, Yangguang Bao, Óscar Monroig, Tingting Zhu, Xie Shichao, Peng Sun, Douglas R Tocher, Qicun Zhou, Min Jin
Background: With the increasing use of high-fat diet (HFD), fatty liver has become prevalent in farmed fish. Leucine regulates lipid metabolism via multiple pathways, but its role in hepatic lipotoxic injury remains unclear.
Objective: This study aimed to determine the molecular mechanism responsible for alleviation of HFD-induced liver injury by dietary supplementation with leucine in black seabream (Acanthopagrus schlegelii).
Methods: In vivo, juvenile black seabream (male; 1.25 ± 0.01 g) were fed 1 of 5 diets in triplicate (30 fish/replicate, n = 3) for 8-wk. The diets consisted of Control (11% lipid) and HFD (18% lipid) diets with the HFD supplemented with 0.5%, 1.0%, or 2.0% leucine. Fish were hand-fed a fixed ration twice daily. Growth, hepatic lipid deposition, and lipotoxic injury were assessed by biochemical, histological, and molecular (flow cytometry, qPCR, and Western blot) methods. In vitro, primary hepatocytes were treated with oleic acid (OA) alone or with 2 mM leucine (n = 3). To explore the mechanism, OA was combined with leucine, Ampk, Sar1b, and Sestrin2 overexpression. Oil Red O staining, immunofluorescence, qPCR, and Western blot assessed lipid accumulation, and signaling pathways. Data were means ± SEM and analyzed by t-test or 1-way analysis of variance, with P < 0.05 considered significant.
Results: In vivo, leucine supplementation activated Sar1b/Sestrin2 and Ampkα1/Sirt1 pathways, reducing HFD-induced hepatic lipid deposition (36%-54%) by enhancing lipolysis (75%-309%) and suppressing lipogenesis (24%-87%). Leucine downregulated ER stress markers (p-Ire1α, 54%-67%) and inhibited p-P65 and p-Jnk (23%-33% and 23%-32%), attenuating inflammation and apoptosis. Similar patterns in vitro confirmed leucine's consistent alleviation of HFD-induced hepatic lipid deposition and lipotoxic injury across models. Overexpression of Ampkα1, Sar1b, or Sestrin2 mimicked leucine's effects, alleviating OA-induced lipid accumulation, inflammation, and apoptosis.
Conclusions: Leucine alleviated HFD-induced liver lipotoxic injury in black seabream by activating Sar1b/Sestrin2 and Ampk1/Sirt1 pathways, providing novel insights for developing nutritional strategies against diet-induced liver injury.
{"title":"Leucine Alleviates Endoplasmic Reticulum-Stress Mediated Lipotoxic Injury Induced by High-Fat Diet Via Sar1b/Sestrin2/Ampkα1 Pathways in Acanthopagrus Schlegelii.","authors":"Wenli Zhao, Yuedong Shen, Xuan Wang, Yangguang Bao, Óscar Monroig, Tingting Zhu, Xie Shichao, Peng Sun, Douglas R Tocher, Qicun Zhou, Min Jin","doi":"10.1016/j.tjnut.2025.101258","DOIUrl":"10.1016/j.tjnut.2025.101258","url":null,"abstract":"<p><strong>Background: </strong>With the increasing use of high-fat diet (HFD), fatty liver has become prevalent in farmed fish. Leucine regulates lipid metabolism via multiple pathways, but its role in hepatic lipotoxic injury remains unclear.</p><p><strong>Objective: </strong>This study aimed to determine the molecular mechanism responsible for alleviation of HFD-induced liver injury by dietary supplementation with leucine in black seabream (Acanthopagrus schlegelii).</p><p><strong>Methods: </strong>In vivo, juvenile black seabream (male; 1.25 ± 0.01 g) were fed 1 of 5 diets in triplicate (30 fish/replicate, n = 3) for 8-wk. The diets consisted of Control (11% lipid) and HFD (18% lipid) diets with the HFD supplemented with 0.5%, 1.0%, or 2.0% leucine. Fish were hand-fed a fixed ration twice daily. Growth, hepatic lipid deposition, and lipotoxic injury were assessed by biochemical, histological, and molecular (flow cytometry, qPCR, and Western blot) methods. In vitro, primary hepatocytes were treated with oleic acid (OA) alone or with 2 mM leucine (n = 3). To explore the mechanism, OA was combined with leucine, Ampk, Sar1b, and Sestrin2 overexpression. Oil Red O staining, immunofluorescence, qPCR, and Western blot assessed lipid accumulation, and signaling pathways. Data were means ± SEM and analyzed by t-test or 1-way analysis of variance, with P < 0.05 considered significant.</p><p><strong>Results: </strong>In vivo, leucine supplementation activated Sar1b/Sestrin2 and Ampkα1/Sirt1 pathways, reducing HFD-induced hepatic lipid deposition (36%-54%) by enhancing lipolysis (75%-309%) and suppressing lipogenesis (24%-87%). Leucine downregulated ER stress markers (p-Ire1α, 54%-67%) and inhibited p-P65 and p-Jnk (23%-33% and 23%-32%), attenuating inflammation and apoptosis. Similar patterns in vitro confirmed leucine's consistent alleviation of HFD-induced hepatic lipid deposition and lipotoxic injury across models. Overexpression of Ampkα1, Sar1b, or Sestrin2 mimicked leucine's effects, alleviating OA-induced lipid accumulation, inflammation, and apoptosis.</p><p><strong>Conclusions: </strong>Leucine alleviated HFD-induced liver lipotoxic injury in black seabream by activating Sar1b/Sestrin2 and Ampk1/Sirt1 pathways, providing novel insights for developing nutritional strategies against diet-induced liver injury.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":"101258"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.tjnut.2025.101318
Ronja H Saarinen , Heli EK Virtanen , Sari Hantunen , Jukka T Salonen , Tomi-Pekka Tuomainen , Jyrki K Virtanen
Background
Metabolic dysfunction–associated steatotic liver disease (MASLD) is the leading cause of liver diseases. Fructose intake has been associated with liver fat accumulation, but less is known whether the associations differ based on the source of fructose.
Objectives
We investigated the cross-sectional and longitudinal associations of intake of total fructose and fructose from different sources with risk of MASLD among middle-aged and older people from Eastern Finland.
Methods
The cross-sectional analyses included 666 males and 865 females aged 53–73 y, examined in 1998–2001. The longitudinal analyses included 300 males and 467 females examined again in 2005–2008. Fructose intake was assessed with 4-d food record. Fatty liver index (FLI) was used as a surrogate for liver fat content. MASLD was defined as FLI ≥60 and the presence of ≥1 cardiometabolic risk factors. Analysis of variance and multivariable-adjusted logistic regression were used for analyses.
Results
The mean total fructose intake was 33 g/d (standard deviation 13.4, 7.4% of the total energy intake), with sweeteners (mainly sugar, 34.5% of the total fructose intake), fruits and berries (20.2%), and beverages (18.9%) being the major sources. In the cross-sectional analyses, participants with higher total fructose intake had 43% lower odds for MASLD [95% confidence interval (CI): 10%, 64%] in those in the highest (>39.7 g/d) compared with the lowest (<24.6 g/d) intake quartile (P-trend across quartiles = 0.02). Among the sources of fructose, the strongest inverse associations were observed with fructose from sweeteners. In the longitudinal analyses, total fructose intake was not associated with MASLD. However, fructose from sweeteners again had a strong inverse association with odds for MASLD (78% lower odds in the highest compared with the lowest quartile, 95% CI: 49%, 90%; P-trend < 0.001). Fructose from fruits and berries or from beverages was not associated with MASLD.
Conclusions
In middle-aged and older Finnish adults, higher fructose intake, especially from sweeteners, was associated with lower odds for MASLD.
{"title":"Associations of Fructose Consumption with Prevalence and Incidence of Metabolic Dysfunction–Associated Steatotic Liver Disease—The Kuopio Ischaemic Heart Disease Risk Factor Study","authors":"Ronja H Saarinen , Heli EK Virtanen , Sari Hantunen , Jukka T Salonen , Tomi-Pekka Tuomainen , Jyrki K Virtanen","doi":"10.1016/j.tjnut.2025.101318","DOIUrl":"10.1016/j.tjnut.2025.101318","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic dysfunction<strong>–</strong>associated steatotic liver disease (MASLD) is the leading cause of liver diseases. Fructose intake has been associated with liver fat accumulation, but less is known whether the associations differ based on the source of fructose.</div></div><div><h3>Objectives</h3><div>We investigated the cross-sectional and longitudinal associations of intake of total fructose and fructose from different sources with risk of MASLD among middle-aged and older people from Eastern Finland.</div></div><div><h3>Methods</h3><div>The cross-sectional analyses included 666 males and 865 females aged 53–73 y, examined in 1998–2001. The longitudinal analyses included 300 males and 467 females examined again in 2005–2008. Fructose intake was assessed with 4-d food record. Fatty liver index (FLI) was used as a surrogate for liver fat content. MASLD was defined as FLI ≥60 and the presence of ≥1 cardiometabolic risk factors. Analysis of variance and multivariable-adjusted logistic regression were used for analyses.</div></div><div><h3>Results</h3><div>The mean total fructose intake was 33 g/d (standard deviation 13.4, 7.4% of the total energy intake), with sweeteners (mainly sugar, 34.5% of the total fructose intake), fruits and berries (20.2%), and beverages (18.9%) being the major sources. In the cross-sectional analyses, participants with higher total fructose intake had 43% lower odds for MASLD [95% confidence interval (CI): 10%, 64%] in those in the highest (>39.7 g/d) compared with the lowest (<24.6 g/d) intake quartile (<em>P</em>-trend across quartiles = 0.02). Among the sources of fructose, the strongest inverse associations were observed with fructose from sweeteners. In the longitudinal analyses, total fructose intake was not associated with MASLD. However, fructose from sweeteners again had a strong inverse association with odds for MASLD (78% lower odds in the highest compared with the lowest quartile, 95% CI: 49%, 90%; <em>P</em>-trend < 0.001). Fructose from fruits and berries or from beverages was not associated with MASLD.</div></div><div><h3>Conclusions</h3><div>In middle-aged and older Finnish adults, higher fructose intake, especially from sweeteners, was associated with lower odds for MASLD.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 2","pages":"Article 101318"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-08DOI: 10.1016/j.tjnut.2025.101260
Rui Su, Xia Zhou, Lyn M Steffen, Chi Chen
Background: Unhealthy diet and microbiota dysbiosis are known risk factors of type 2 diabetes (T2D), but the value of microbial metabolites as indicators of diet quality and T2D risk has rarely been explored.
Objectives: In this prospective study, we examined the correlations of dietary intake and circulating microbial metabolism-associated metabolites with T2D parameters in adults enrolled in the Coronary Artery Risk Development in Young Adults study.
Methods: A cohort of 2296 nondiabetic participants was examined on their diet quality, plasma metabolome, fasting glucose, and insulin in year 7 of the coronary artery risk development in young adults study, and the occurrence of incident T2D afterward. Dietary intake was assessed by an interviewer-administered diet history. Diet quality was characterized by the Healthy Eating Index 2020 score. Spearman correlation analysis assessed the associations of plasma metabolites with healthy eating index, fasting glucose, insulin, and homeostatic model assessment indexes. Subsequent propensity matching of 131 incident T2D cases with controls yielded a paired dataset for logistic and multivariate regression analyses, resulting in the predictive markers that were further validated by Cox proportional hazard models on 3 random cohorts selected from the full cohort.
Results: Among 611 circulating plasma metabolites, 41 were classified as microbial metabolites or their dietary precursors. Cinnamoylglycine, a metabolite produced jointly by microbial phenylalanine fermentation and hepatic glycine conjugation, was positively correlated with diet quality and inversely associated with incident T2D risk [odds ratio (OR): 0.66; 95% confidence interval (CI): 0.49, 0.87]. Isoleucine was inversely correlated with diet quality and positively associated with T2D risk (OR: 1.98; 95% CI: 1.36, 2.87). This contrast between cinnamoylglycine and isoleucine provided a cinnamoylglycine/isoleucine ratio as a predictive indicator of diet quality and incident T2D risk (OR: 0.61; 95% CI: 0.46, 0.82), which was validated from the 3 randomly selected samples (hazard ratio: 0.75; 95% CI: 0.59, 0.96; P = 0.02).
Conclusions: The cinnamoylglycine/isoleucine ratio may be an effective indicator linking diet quality, microbial metabolism, and T2D risk.
背景：不健康的饮食和微生物群失调是已知的2型糖尿病（T2D）的危险因素，但微生物代谢物作为饮食质量和T2D风险指标的价值很少被探索。目的：在这项前瞻性研究中，我们研究了参加年轻人冠状动脉风险发展（CARDIA）研究的成年人的饮食摄入和循环微生物代谢相关代谢物与T2D参数的相关性。方法：在CARDIA研究的第7年，研究了2296名非糖尿病参与者的饮食质量、血浆代谢组、空腹血糖和胰岛素，以及之后T2D事件的发生情况。膳食摄入量通过访谈者管理的饮食史进行评估。饮食质量以健康饮食指数2020 （HEI）评分为特征。Spearman相关分析评估血浆代谢物与HEI、空腹血糖、胰岛素和稳态模型评估（HOMA）指标的关系。随后将131例T2D病例与对照组进行倾向匹配，产生了用于逻辑和多变量回归分析的配对数据集，并通过从全队列中选择的三个随机队列的Cox比例风险模型进一步验证了预测标记。结果：在611种循环血浆代谢物中，有41种被归类为微生物代谢物或其膳食前体。肉桂酰甘氨酸是微生物苯丙氨酸发酵和肝甘氨酸偶联共同产生的代谢物，与饮食质量正相关，与T2D发病风险负相关（比值比[OR] =0.66; 95% ci = 0.49, 0.87）。异亮氨酸与饮食质量呈负相关，与T2D风险呈正相关（OR=1.98; 95% ci = 1.36, 2.87）。肉桂酰甘氨酸和异亮氨酸之间的对比提供了肉桂酰甘氨酸/异亮氨酸（C/I）比率作为饮食质量和T2D事件风险的预测指标（OR=0.61; 95% ci = 0.46, 0.82），并在三个随机选择的样本中得到验证（风险比[HR]=0.75; 95% ci = 0.59, 0.96; p=0.02）。结论：C/I比值可能是联系饮食质量、微生物代谢和T2D风险的有效指标。临床试验注册编号和获取的网站：不适用。
{"title":"Identifying the Ratio of Circulating Cinnamoylglycine to Isoleucine as a Biomarker Linking Diet Quality, Microbial Metabolism, and Type 2 Diabetes Risk in the Coronary Artery Risk Development in Young Adults (CARDIA) Cohorts.","authors":"Rui Su, Xia Zhou, Lyn M Steffen, Chi Chen","doi":"10.1016/j.tjnut.2025.101260","DOIUrl":"10.1016/j.tjnut.2025.101260","url":null,"abstract":"<p><strong>Background: </strong>Unhealthy diet and microbiota dysbiosis are known risk factors of type 2 diabetes (T2D), but the value of microbial metabolites as indicators of diet quality and T2D risk has rarely been explored.</p><p><strong>Objectives: </strong>In this prospective study, we examined the correlations of dietary intake and circulating microbial metabolism-associated metabolites with T2D parameters in adults enrolled in the Coronary Artery Risk Development in Young Adults study.</p><p><strong>Methods: </strong>A cohort of 2296 nondiabetic participants was examined on their diet quality, plasma metabolome, fasting glucose, and insulin in year 7 of the coronary artery risk development in young adults study, and the occurrence of incident T2D afterward. Dietary intake was assessed by an interviewer-administered diet history. Diet quality was characterized by the Healthy Eating Index 2020 score. Spearman correlation analysis assessed the associations of plasma metabolites with healthy eating index, fasting glucose, insulin, and homeostatic model assessment indexes. Subsequent propensity matching of 131 incident T2D cases with controls yielded a paired dataset for logistic and multivariate regression analyses, resulting in the predictive markers that were further validated by Cox proportional hazard models on 3 random cohorts selected from the full cohort.</p><p><strong>Results: </strong>Among 611 circulating plasma metabolites, 41 were classified as microbial metabolites or their dietary precursors. Cinnamoylglycine, a metabolite produced jointly by microbial phenylalanine fermentation and hepatic glycine conjugation, was positively correlated with diet quality and inversely associated with incident T2D risk [odds ratio (OR): 0.66; 95% confidence interval (CI): 0.49, 0.87]. Isoleucine was inversely correlated with diet quality and positively associated with T2D risk (OR: 1.98; 95% CI: 1.36, 2.87). This contrast between cinnamoylglycine and isoleucine provided a cinnamoylglycine/isoleucine ratio as a predictive indicator of diet quality and incident T2D risk (OR: 0.61; 95% CI: 0.46, 0.82), which was validated from the 3 randomly selected samples (hazard ratio: 0.75; 95% CI: 0.59, 0.96; P = 0.02).</p><p><strong>Conclusions: </strong>The cinnamoylglycine/isoleucine ratio may be an effective indicator linking diet quality, microbial metabolism, and T2D risk.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":"101260"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145723995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.tjnut.2025.101313
Martha A Belury
{"title":"Sowing Seed Oil Science: Rationale for Dose Testing for Essential Nutrients.","authors":"Martha A Belury","doi":"10.1016/j.tjnut.2025.101313","DOIUrl":"https://doi.org/10.1016/j.tjnut.2025.101313","url":null,"abstract":"","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 2","pages":"101313"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.tjnut.2025.101288
Rachel M Cole , Eric Colombo , Austin Angelotti , Genevieve C Sparagna , Rolando E Choriego , Rafael Jimenez-Flores , Andy Ni , Martha A Belury
Background
Linoleic acid biomarkers are associated with positive health outcomes including lower risk of diabetes and cardiovascular disease. The effect of consuming linoleate-fortified foods (compared with palm oil-fortified foods) in a randomized controlled, double-masked crossover study to change linoleic acid biomarkers without changing bodyweight is unknown.
Objectives
The aim of this study was to determine the effect of delivering soybean and palm oils through foods on the linoleic acid content of blood fractions and body weight in adults.
Methods
In this crossover pilot study, 4 male and 6 female adults, ages 25–76 y and body mass index from 26 to 41 kg/m2, were randomly assigned to consume: 30 g of soybean and palm oil delivered in 3 study foods/d for 4 wk separated by a 2-wk washout period. Bodyweight, fatty acid profile of plasma, erythrocytes, peripheral blood mononuclear cells (PBMC), and dried blood spots, and PBMC cardiolipin were measured before and after each intervention period. Dietary intake was assessed using 24-h recalls. The outcomes were analyzed using the Wilcoxon Signed Rank Test.
Results
After 4 wk of consuming 3 foods/d, plasma linoleic acid decreased during the palm oil intervention (–1.60, P = 0.04), whereas it tended to increase in plasma (2.35, P = 0.07) and erythrocytes (1.09, P = 0.05) during the soybean oil intervention. The percentage of PBMC tetralinoleoyl cardiolipin marginally increased during the soybean oil intervention (2.31, P = 0.05) but did not change during the palm oil intervention. There was no difference in energy intake between the 2 interventions (P = 0.65) and no change in bodyweight during either intervention (P > 0.40).
Conclusions
Foods can be used to deliver 30 g/d of dietary oil for 4 wk to impact linoleic acid biomarkers without incurring body weight changes. These foods are useful for future randomized controlled double-masked clinical trials assessing the impact of dietary oils on energy metabolism.
The study was registered at clinicaltrials.gov as NCT04975763 (https://clinicaltrials.gov/study/NCT04975763).
{"title":"Feasibility Study of Soybean Oil-Fortified Foods to Alter Blood Content of Linoleic Acid and Body Weight: A Randomized Double-Masked Placebo-Controlled Crossover Trial","authors":"Rachel M Cole , Eric Colombo , Austin Angelotti , Genevieve C Sparagna , Rolando E Choriego , Rafael Jimenez-Flores , Andy Ni , Martha A Belury","doi":"10.1016/j.tjnut.2025.101288","DOIUrl":"10.1016/j.tjnut.2025.101288","url":null,"abstract":"<div><h3>Background</h3><div>Linoleic acid biomarkers are associated with positive health outcomes including lower risk of diabetes and cardiovascular disease. The effect of consuming linoleate-fortified foods (compared with palm oil-fortified foods) in a randomized controlled, double-masked crossover study to change linoleic acid biomarkers without changing bodyweight is unknown.</div></div><div><h3>Objectives</h3><div>The aim of this study was to determine the effect of delivering soybean and palm oils through foods on the linoleic acid content of blood fractions and body weight in adults.</div></div><div><h3>Methods</h3><div>In this crossover pilot study, 4 male and 6 female adults, ages 25–76 y and body mass index from 26 to 41 kg/m<sup>2</sup>, were randomly assigned to consume: 30 g of soybean and palm oil delivered in 3 study foods/d for 4 wk separated by a 2-wk washout period. Bodyweight, fatty acid profile of plasma, erythrocytes, peripheral blood mononuclear cells (PBMC), and dried blood spots, and PBMC cardiolipin were measured before and after each intervention period. Dietary intake was assessed using 24-h recalls. The outcomes were analyzed using the Wilcoxon Signed Rank Test.</div></div><div><h3>Results</h3><div>After 4 wk of consuming 3 foods/d, plasma linoleic acid decreased during the palm oil intervention (–1.60, <em>P</em> = 0.04), whereas it tended to increase in plasma (2.35, <em>P</em> = 0.07) and erythrocytes (1.09, <em>P</em> = 0.05) during the soybean oil intervention. The percentage of PBMC tetralinoleoyl cardiolipin marginally increased during the soybean oil intervention (2.31, <em>P</em> = 0.05) but did not change during the palm oil intervention. There was no difference in energy intake between the 2 interventions (<em>P</em> = 0.65) and no change in bodyweight during either intervention (<em>P</em> > 0.40).</div></div><div><h3>Conclusions</h3><div>Foods can be used to deliver 30 g/d of dietary oil for 4 wk to impact linoleic acid biomarkers without incurring body weight changes. These foods are useful for future randomized controlled double-masked clinical trials assessing the impact of dietary oils on energy metabolism.</div><div>The study was registered at <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> as NCT04975763 (<span><span>https://clinicaltrials.gov/study/NCT04975763</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 2","pages":"Article 101288"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145856363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-08DOI: 10.1016/j.tjnut.2025.101265
Ezgi Cengiz
{"title":"Which Sodium Reduction Policies Work, and for Whom?","authors":"Ezgi Cengiz","doi":"10.1016/j.tjnut.2025.101265","DOIUrl":"10.1016/j.tjnut.2025.101265","url":null,"abstract":"","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":"101265"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.tjnut.2025.101316
Anaëlle Bolo , Sarah Chabert , Marion Salomé , Eric O Verger , Hélène Fouillet , François Mariotti
Background
Dietary diversity is essential for nutrient adequacy, but its effects may vary depending on which food groups are diversified and the dimension of diversity considered (i.e., the number of food subgroups consumed, their consumption evenness, or their nutritional dissimilarity).
Objectives
This study aimed to identify which food groups and diversity dimensions contribute to positive or negative effects of dietary diversity on the nutrient quality of diets, and to assess the magnitude of these effects and their underlying mechanisms.
Methods
Using data from the French National Food Consumption Survey, we developed an individual-level microsimulation model to maximize diversity within 12 food groups—one at a time—either in a single dimension or across the 3 dimensions simultaneously, while keeping the total quantity consumed constant. Nutrient quality was evaluated using probabilistic scores for nutrient adequacy, nutrient security (i.e., risk of deficiency), and moderation (i.e., avoidance of excessive intakes of sugar, sodium, and saturated fat). The effects of increasing diversity were analyzed using factorial repeated-measures analysis of variance.
Results
Five food groups categories emerged based on how increased within-group diversity impacted nutrient quality: “favorable,” “no effect, “mixed effects,” “highly contrasting effects,” and “unfavorable.” “Vegetables,” “Fish and Seafood,” and “Bread” food groups fell into the first category, where greater diversity enhanced nutrient adequacy (with effect sizes ranging from +0.04 to +0.16 SD) without compromising moderation. In these cases, increasing the number of subgroups consumed was the most effective strategy. In contrast, increasing diversity within “Meat, Poultry, Eggs” and “Dairy,” classified under the contrasting or unfavorable categories, tended to undermine moderation (from –0.05 to –0.20 SD). These negative effects were primarily driven by increasing consumption evenness and nutrient dissimilarity.
Conclusions
Promoting dietary diversity should not be generic. It should be targeted to the food group and diversification strategies that enhance nutrient adequacy without compromising moderation.
{"title":"Benefits of Increased Dietary Diversity Depend on Food Group and Diversity Dimension: A Microsimulation Modeling Study","authors":"Anaëlle Bolo , Sarah Chabert , Marion Salomé , Eric O Verger , Hélène Fouillet , François Mariotti","doi":"10.1016/j.tjnut.2025.101316","DOIUrl":"10.1016/j.tjnut.2025.101316","url":null,"abstract":"<div><h3>Background</h3><div>Dietary diversity is essential for nutrient adequacy, but its effects may vary depending on which food groups are diversified and the dimension of diversity considered (i.e., the number of food subgroups consumed, their consumption evenness, or their nutritional dissimilarity).</div></div><div><h3>Objectives</h3><div>This study aimed to identify which food groups and diversity dimensions contribute to positive or negative effects of dietary diversity on the nutrient quality of diets, and to assess the magnitude of these effects and their underlying mechanisms.</div></div><div><h3>Methods</h3><div>Using data from the French National Food Consumption Survey, we developed an individual-level microsimulation model to maximize diversity within 12 food groups—one at a time—either in a single dimension or across the 3 dimensions simultaneously, while keeping the total quantity consumed constant. Nutrient quality was evaluated using probabilistic scores for nutrient adequacy, nutrient security (i.e., risk of deficiency), and moderation (i.e., avoidance of excessive intakes of sugar, sodium, and saturated fat). The effects of increasing diversity were analyzed using factorial repeated-measures analysis of variance.</div></div><div><h3>Results</h3><div>Five food groups categories emerged based on how increased within-group diversity impacted nutrient quality: “favorable,” “no effect, “mixed effects,” “highly contrasting effects,” and “unfavorable.” “Vegetables,” “Fish and Seafood,” and “Bread” food groups fell into the first category, where greater diversity enhanced nutrient adequacy (with effect sizes ranging from +0.04 to +0.16 SD) without compromising moderation. In these cases, increasing the number of subgroups consumed was the most effective strategy. In contrast, increasing diversity within “Meat, Poultry, Eggs” and “Dairy,” classified under the contrasting or unfavorable categories, tended to undermine moderation (from –0.05 to –0.20 SD). These negative effects were primarily driven by increasing consumption evenness and nutrient dissimilarity.</div></div><div><h3>Conclusions</h3><div>Promoting dietary diversity should not be generic. It should be targeted to the food group and diversification strategies that enhance nutrient adequacy without compromising moderation.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 2","pages":"Article 101316"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-09DOI: 10.1016/j.tjnut.2025.101266
Emma Huijgen, Hanneke Ah Wijnhoven, Marjolein Visser
Background: Although plant proteins have less environmental impact than animal proteins, it remains unclear whether they can adequately support physical functioning in old age.
Objective: This prospective study aimed to investigate the association of the dietary plant-to-animal protein intake ratio with the incidence of slow gait speed among older adults.
Methods: Data from 997 adults [50.7% male, mean age 65.5 (SD 6.9) y] with a baseline gait speed ≥0.8 m/s were derived from the Longitudinal Aging Study Amsterdam. The dietary plant-to-animal protein intake ratio was calculated from a 238-item food frequency questionnaire completed from 2014 to 2015. Gait speed was measured at baseline and at three 3-y follow-up waves using a 6-meter walk test. Cox proportional hazards models estimated the association between protein ratio quintiles and incident slow gait speed (<0.8 m/s), while adjusting for demographic and lifestyle factors and testing for interaction by sex, overall diet quality, protein intake, and baseline gait speed.
Results: The median dietary plant-to-animal protein intake ratio was 0.67 [interquartile range (IQR): 0.52 to 0.86]. During follow-up, slow gait speed (<0.8 m/s) developed in 415 participants (41.6%). No significant association was found between the protein ratio and incident slow gait speed. The adjusted hazard ratio of the highest (ratio > 0.91) compared with the lowest (ratio ≤ 0.49) quintile was 0.98 (95% confidence interval: 0.68, 1.42; trend across quintiles P = 0.89). No significant interactions were observed with sex, overall diet quality, or total protein intake. A higher plant-to-animal protein ratio was suggested to be associated with a lower risk of incident slow gait speed in those with relatively faster baseline gait speed, although associations were not statistically significant.
Conclusions: Among Dutch older adults, the dietary plant-to-animal protein intake ratio was not associated with the risk of developing slow gait speed, suggesting that a more sustainable diet including higher plant protein intake may not compromise physical functioning in older adults.
{"title":"Association of the Dietary Plant-To-Animal Protein Intake Ratio with the Incidence of Slow Gait Speed in Older Adults.","authors":"Emma Huijgen, Hanneke Ah Wijnhoven, Marjolein Visser","doi":"10.1016/j.tjnut.2025.101266","DOIUrl":"10.1016/j.tjnut.2025.101266","url":null,"abstract":"<p><strong>Background: </strong>Although plant proteins have less environmental impact than animal proteins, it remains unclear whether they can adequately support physical functioning in old age.</p><p><strong>Objective: </strong>This prospective study aimed to investigate the association of the dietary plant-to-animal protein intake ratio with the incidence of slow gait speed among older adults.</p><p><strong>Methods: </strong>Data from 997 adults [50.7% male, mean age 65.5 (SD 6.9) y] with a baseline gait speed ≥0.8 m/s were derived from the Longitudinal Aging Study Amsterdam. The dietary plant-to-animal protein intake ratio was calculated from a 238-item food frequency questionnaire completed from 2014 to 2015. Gait speed was measured at baseline and at three 3-y follow-up waves using a 6-meter walk test. Cox proportional hazards models estimated the association between protein ratio quintiles and incident slow gait speed (<0.8 m/s), while adjusting for demographic and lifestyle factors and testing for interaction by sex, overall diet quality, protein intake, and baseline gait speed.</p><p><strong>Results: </strong>The median dietary plant-to-animal protein intake ratio was 0.67 [interquartile range (IQR): 0.52 to 0.86]. During follow-up, slow gait speed (<0.8 m/s) developed in 415 participants (41.6%). No significant association was found between the protein ratio and incident slow gait speed. The adjusted hazard ratio of the highest (ratio > 0.91) compared with the lowest (ratio ≤ 0.49) quintile was 0.98 (95% confidence interval: 0.68, 1.42; trend across quintiles P = 0.89). No significant interactions were observed with sex, overall diet quality, or total protein intake. A higher plant-to-animal protein ratio was suggested to be associated with a lower risk of incident slow gait speed in those with relatively faster baseline gait speed, although associations were not statistically significant.</p><p><strong>Conclusions: </strong>Among Dutch older adults, the dietary plant-to-animal protein intake ratio was not associated with the risk of developing slow gait speed, suggesting that a more sustainable diet including higher plant protein intake may not compromise physical functioning in older adults.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":"101266"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.tjnut.2025.101280
Mary A Uyoga , Jeannine Baumgartner , Linda Malan , Angélique Lewies , Lizelle Zandberg , Christophe Zeder , Cornelius M Smuts , Isabelle Herter-Aeberli
Background
Young South African women face a double-burden of overweight or obesity and iron deficiency, with the former predicting the latter. Omega-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation can reduce inflammation. It is uncertain if this effect extends to adiposity-related inflammation, thereby reducing hepcidin secretion and improving iron absorption.
Objectives
Using stable iron isotopes, we determined the effect of omega-3 LCPUFA supplementation on fractional iron absorption (FIA) from a meal containing iron as ferrous sulfate without and with ascorbic acid (AA).
Methods
In this single-blind, uncontrolled, before–after intervention stable isotope study, 30 South African women aged 18–35 y with body mass index ≥28 kg/m2, systemic inflammation, and a low omega-3 LCPUFA status, consumed a noninhibitory meal containing 6 mg iron, without and with AA, before and after 3 mo of daily supplementation with 2.1 g omega-3 LCPUFA. At baseline and endpoint, we measured FIA 14 d after consumption of the second meal, iron and inflammation markers, hepcidin, and omega-3 index.
Results
At baseline and endpoint, addition of AA significantly improved FIA from the meal. Median (IQR) FIA before compared with after supplementation was not different for the meal without AA [9.7 (4.3–24.6)% compared with 11.8 (2.8–22.3)%; P = 0.962] nor the meal with AA [27.5 (10.6–43.8)% compared with 30.8 (9.6–60.9)%; P = 0.249]. Supplementation increased the omega-3 index from 4.61 (4.10–5.11)% to 5.97 (5.48–8.16)% (P < 0.001), but did not reduce hepcidin or improve the inflammation and iron status markers. In multiple linear regression analyses, hepcidin was a stronger predictor of FIA than AA.
Conclusions
Addition of AA to the test meal, rather than omega-3 LCPUFA supplementation, improved iron absorption in South African women with overweight or obesity. Despite an increase in omega-3 index after omega-3 LCPUFA supplementation, it remained suboptimal, possibly explaining the lack of reduction in inflammation and hepcidin concentrations.
This study was registered at clinicaltrials.gov as NCT05220735 (https://clinicaltrials.gov/study/NCT05220735?cond=obesity&term=iron%20absorption&rank=4).
背景：年轻的南非女性面临着超重或肥胖和缺铁的双重负担，前者预示着后者。补充Omega-3长链多不饱和脂肪酸（LCPUFA）可以减少炎症。目前尚不确定这种效应是否延伸到肥胖相关炎症，从而减少hepcidin分泌并改善铁的吸收。目的：利用稳定的铁同位素，我们测定了补充omega-3 LCPUFA对含铁膳食中铁的分数吸收（FIA）的影响，如不含和含抗坏血酸（AA）的硫酸亚铁。方法：在这项单盲、无控制、干预前后稳定同位素研究中，30名年龄在18-35岁、体重指数≥28 kg/m2、全身性炎症、omega-3 LCPUFA水平低的南非女性，在每天补充2.1 g omega-3 LCPUFA三个月之前和之后，食用含6 mg铁的非抑制性膳食，不含AA和含AA。在基线和终点，我们测量了进食第二餐后14天的FIA、铁和炎症标志物、hepcidin和omega-3指数。结果：在基线和终点，添加AA显著改善了饲料中的FIA。不添加AA的饲料(9.7 （4.3-24.6)% vs. 11.8 (2.8-22.3)%, p=0.962）和添加AA的饲料(27.5 (10.6-43.8)% vs. 30.8(9.6-60.9)%)，添加前后的中位FIA （IQR）无差异；p = 0.249)。补充omega-3指数从4.61(4.10-5.11)%增加到5.97(5.48-8.16)%。结论：在试验餐中添加AA，而不是补充omega-3 LCPUFA，可以改善南非超重或肥胖妇女的铁吸收。尽管补充omega-3 LCPUFA后omega-3指数有所增加，但仍处于次优状态，这可能解释了炎症和hepcidin水平缺乏降低的原因。临床试验注册号：NCT05220735 （https://clinicaltrials.gov/study/NCT05220735?cond=obesity&term=iron%20absorption&rank=4）。
{"title":"Omega-3 Long-Chain Polyunsaturated Fatty Acid Supplementation Did Not Reduce Inflammation to Improve Iron Absorption in South African Women Living with Overweight or Obesity","authors":"Mary A Uyoga , Jeannine Baumgartner , Linda Malan , Angélique Lewies , Lizelle Zandberg , Christophe Zeder , Cornelius M Smuts , Isabelle Herter-Aeberli","doi":"10.1016/j.tjnut.2025.101280","DOIUrl":"10.1016/j.tjnut.2025.101280","url":null,"abstract":"<div><h3>Background</h3><div>Young South African women face a double-burden of overweight or obesity and iron deficiency, with the former predicting the latter. Omega-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation can reduce inflammation. It is uncertain if this effect extends to adiposity-related inflammation, thereby reducing hepcidin secretion and improving iron absorption.</div></div><div><h3>Objectives</h3><div>Using stable iron isotopes, we determined the effect of omega-3 LCPUFA supplementation on fractional iron absorption (FIA) from a meal containing iron as ferrous sulfate without and with ascorbic acid (AA).</div></div><div><h3>Methods</h3><div>In this single-blind, uncontrolled, before–after intervention stable isotope study, 30 South African women aged 18–35 y with body mass index ≥28 kg/m<sup>2</sup><sub>,</sub> systemic inflammation, and a low omega-3 LCPUFA status, consumed a noninhibitory meal containing 6 mg iron, without and with AA, before and after 3 mo of daily supplementation with 2.1 g omega-3 LCPUFA. At baseline and endpoint, we measured FIA 14 d after consumption of the second meal, iron and inflammation markers, hepcidin, and omega-3 index.</div></div><div><h3>Results</h3><div>At baseline and endpoint, addition of AA significantly improved FIA from the meal. Median (IQR) FIA before compared with after supplementation was not different for the meal without AA [9.7 (4.3–24.6)% compared with 11.8 (2.8–22.3)%; <em>P</em> = 0.962] nor the meal with AA [27.5 (10.6–43.8)% compared with 30.8 (9.6–60.9)%; <em>P</em> = 0.249]. Supplementation increased the omega-3 index from 4.61 (4.10–5.11)% to 5.97 (5.48–8.16)% (<em>P</em> < 0.001), but did not reduce hepcidin or improve the inflammation and iron status markers. In multiple linear regression analyses, hepcidin was a stronger predictor of FIA than AA.</div></div><div><h3>Conclusions</h3><div>Addition of AA to the test meal, rather than omega-3 LCPUFA supplementation, improved iron absorption in South African women with overweight or obesity. Despite an increase in omega-3 index after omega-3 LCPUFA supplementation, it remained suboptimal, possibly explaining the lack of reduction in inflammation and hepcidin concentrations.</div><div>This study was registered at <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> as NCT05220735 (<span><span>https://clinicaltrials.gov/study/NCT05220735?cond=obesity&term=iron%20absorption&rank=4</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 2","pages":"Article 101280"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.tjnut.2025.101289
Kai-Yang Chen , Hoi-Chun Chan , Chi-Ming Chan
<div><h3>Background</h3><div>Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. While anti-vascular endothelial growth factor (anti-VEGF) therapies are available for neovascular AMD (nAMD), effective preventive strategies remain limited. Long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have biological plausibility for retinal protection through structural roles in photoreceptor membranes and anti-inflammatory lipid mediator pathways.</div></div><div><h3>Objectives</h3><div>This study aimed to synthesize contemporary evidence regarding omega-3 fatty acids in AMD prevention, with emphasis on subtype-specific associations, differences by omega-3 species, and contrasts between dietary intake and supplementation evidence.</div></div><div><h3>Methods</h3><div>This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidance and registered the protocol in PROSPERO (CRD420251122413). PubMed, ScienceDirect, and the Cochrane Library were searched from inception to August 2, 2025. Eligible studies included observational studies of dietary ω-3 PUFA exposure in adults aged 50 years or older with AMD outcomes. Random-effects models models were used to pool adjusted effect estimates comparing the highest versus lowest ω-3 exposure categories. Prespecified subgroup analyses were performed by AMD subtype (early AMD, advanced AMD, nAMD, and geographic atrophy [GA]) and ω-3 species (EPA, DHA, and alpha-linolenic acid [ALA]). Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS). Publication bias was evaluated using funnel plots and Egger’s regression test.</div></div><div><h3>Results</h3><div>Eighteen studies were included. Higher ω-3 intake was associated with reduced odds of AMD overall (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70–0.96; p = 0.01), with moderate heterogeneity (<em>I</em>² = 61%). Subtype analyses demonstrated stronger associations for nAMD (OR 0.57, 95% CI 0.40–0.81) and GA (OR 0.65, 95% CI 0.45–0.94), and a smaller association for early AMD (OR 0.83, 95% CI 0.72–0.97), whereas advanced AMD was not significantly different between high and low intake groups (OR 0.81, 95% CI 0.49–1.33; p = 0.41). In ω-3 species analyses, higher EPA intake was associated with lower AMD odds (OR 0.61, 95% CI 0.38–0.97; p = 0.04), while DHA showed a borderline association (OR 0.73, 95% CI 0.53–1.01; p = 0.05); ALA was not associated with benefit (OR 1.00, 95% CI 0.84–1.20; p = 0.96). Time-to-event pooling showed no significant long-term risk reduction (hazard ratio [HR] 0.98, 95% CI 0.84–1.15; p = 0.83). Funnel plot asymmetry was observed, and Egger’s test suggested small-study effects (p = 0.04).</div></div><div><h3>Conclusions</h3><div>Higher dietary intake of marine-derived ω-3 PUFAs is associated with reduced odds of AMD. However, long-term risk reduction was not demonst
{"title":"Can Omega-3 Fatty Acids Serve as a Preventive Strategy for Age-Related Macular Degeneration? A Systematic Review and Meta-Analysis","authors":"Kai-Yang Chen , Hoi-Chun Chan , Chi-Ming Chan","doi":"10.1016/j.tjnut.2025.101289","DOIUrl":"10.1016/j.tjnut.2025.101289","url":null,"abstract":"<div><h3>Background</h3><div>Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. While anti-vascular endothelial growth factor (anti-VEGF) therapies are available for neovascular AMD (nAMD), effective preventive strategies remain limited. Long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have biological plausibility for retinal protection through structural roles in photoreceptor membranes and anti-inflammatory lipid mediator pathways.</div></div><div><h3>Objectives</h3><div>This study aimed to synthesize contemporary evidence regarding omega-3 fatty acids in AMD prevention, with emphasis on subtype-specific associations, differences by omega-3 species, and contrasts between dietary intake and supplementation evidence.</div></div><div><h3>Methods</h3><div>This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidance and registered the protocol in PROSPERO (CRD420251122413). PubMed, ScienceDirect, and the Cochrane Library were searched from inception to August 2, 2025. Eligible studies included observational studies of dietary ω-3 PUFA exposure in adults aged 50 years or older with AMD outcomes. Random-effects models models were used to pool adjusted effect estimates comparing the highest versus lowest ω-3 exposure categories. Prespecified subgroup analyses were performed by AMD subtype (early AMD, advanced AMD, nAMD, and geographic atrophy [GA]) and ω-3 species (EPA, DHA, and alpha-linolenic acid [ALA]). Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS). Publication bias was evaluated using funnel plots and Egger’s regression test.</div></div><div><h3>Results</h3><div>Eighteen studies were included. Higher ω-3 intake was associated with reduced odds of AMD overall (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70–0.96; p = 0.01), with moderate heterogeneity (<em>I</em>² = 61%). Subtype analyses demonstrated stronger associations for nAMD (OR 0.57, 95% CI 0.40–0.81) and GA (OR 0.65, 95% CI 0.45–0.94), and a smaller association for early AMD (OR 0.83, 95% CI 0.72–0.97), whereas advanced AMD was not significantly different between high and low intake groups (OR 0.81, 95% CI 0.49–1.33; p = 0.41). In ω-3 species analyses, higher EPA intake was associated with lower AMD odds (OR 0.61, 95% CI 0.38–0.97; p = 0.04), while DHA showed a borderline association (OR 0.73, 95% CI 0.53–1.01; p = 0.05); ALA was not associated with benefit (OR 1.00, 95% CI 0.84–1.20; p = 0.96). Time-to-event pooling showed no significant long-term risk reduction (hazard ratio [HR] 0.98, 95% CI 0.84–1.15; p = 0.83). Funnel plot asymmetry was observed, and Egger’s test suggested small-study effects (p = 0.04).</div></div><div><h3>Conclusions</h3><div>Higher dietary intake of marine-derived ω-3 PUFAs is associated with reduced odds of AMD. However, long-term risk reduction was not demonst","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 2","pages":"Article 101289"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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